Introduction
Methods
Search strategy
Study selection
Data extraction
Statistical analyses
Results
Author, year, country (ref) | Study name, characteristics | Follow-up period (years of follow-up) | Study size, sex, number of cases | Dietary assessment | Outcome | Quantity | RR | Adjustment for confounders |
---|---|---|---|---|---|---|---|---|
Esophageal cancer
| ||||||||
Steevens 2011, Netherlands [26] | NLCS Case cohort Age: 55–69 years | 1986–2002 (16.3) | 4 035 Men and women, 144 | Validated FFQ, 150 food items, fresh lemon juice, grapefruits, grapefruit juice, mandarins, oranges, fresh orange juice | Incidence Esophageal AC | 156 versus 0 g/day Per 25 g/day | 0.55 (0.31–0.98) Ptrend: 0.37 0.97 (0.90–1.04) | Age, sex, smoking status, cigarettes/day, smoking duration, alcohol, red meat, fish, vegetable, all other fruits |
101 | Esophageal SCC | 156 versus 0 g/day Per 25 g/day | 0.54 (0.27–1.07) Ptrend: 0.38 1.01 (0.92–1.10) | |||||
Li, 2010, Japan [25] | NHI Prospective Cohort Age: 40–79 years | 1995–2003 (9) | 42,470 Men and women, 151 | Validated FFQ, 40 food items, citrus fruit | Incidence Esophageal cancer | ≥7 versus ≤2 times/week | 0.71 (0.43–1.16) Ptrend: 0.18 | Age, sex, BMI, smoking, alcohol, employment, education, walking, exercise or sports, diabetes, gastric ulcer, hypertension, family history of cancer, energy intake, intake of tea, coffee, miso soup, rice, soybean, dairy products, fish, meat, vegetables, and other fruits |
Yamaji, 2008, Japan [27] | JPHC Prospective Cohort Age: 40–69 years | 1995/1998–2004 (7.7) | 38 790 Men, 116 | Validated FFQ, 138 food and beverage items, mandarin oranges, other oranges, 100 % orange juice | Incidence Esophageal SCC | 127 versus 10 g/day Per 100 g/day | 0.78 (0.48–1.25) 0.89 (0.66–1.20) | Age, study area, cigarette smoking, alcohol drinking |
Freedman, 2007, USA [16] | NIH-AARP Prospective Cohort Age: 50 years | 1995/1996–2000 (4.5) | 490,802 Men and women, 213 | Validated FFQ, 124 food items, oranges, tangerines, tangelos, grapefruits | Incidence Esophageal AC | 1.12 versus 0.08 serving/ 1,000 kcal | 0.96 (0.69–1.35) | Age, sex, BMI, alcohol, education, smoking dose, total energy intake, usual activity throughout the day, vigorous physical activity |
103 | Esophageal SCC | 0.58 (0.34–0. 99) Ptrend: 0.05 | ||||||
Iso, 2007, Japan [24] | JACC Prospective cohort Age: 40–79 years | N/A-2003 (15) | 43,011 Men, 139 | Validated FFQ, 39 food items, citrus fruit | Mortality Esophageal cancer | ≥5 versus < 3 times/week | 1.18 (0.73–1.89) | Age, area of study |
59 504 Women, 25 | 0.80 (0.30–2.11) | |||||||
González, 2006, 10 European countries [18] | EPIC Prospective cohort Age: 35–70 years | 1992/1998–2002 (6.5) | 481 518 Men and women, 67 | Country-specific validated questionnaires, 88–266 items; food record, citrus fruit, juices excluded | Incidence Esophageal AC | ≥43.40 versus ≤10.68 g/day (M) ≥60.71 versus ≤17.43 g/day (W) Per 50 g/day | 0.73 (0.39–1.37) Ptrend: 0.22 (observed) 0.77 (0.46–1.28) (calibrated) | Age, sex, center, education level, energy intake, height, leisure, physical activity, red meat intake, weight, work, physical activity, alcohol intake, processed meat intake, smoking |
Author, year, country (ref) | Study name, characteristics | Follow-up period (years of follow-up) | Study size, sex, number of cases | Dietary assessment | Outcome | Quantity | RR | Adjustment for confounders |
Gastric cancer
| ||||||||
González, 2012, 10 European countries [19] | EPIC Prospective Cohort Age: 35–70 years | 1992/1998–2010 (11.02) 240 206 225 | 477 312 Men and women, 683 | Country-specific validated questionnaires, 88–266 items; food record, citrus fruit, juices excluded | Incidence Gastric AC | 103.6 versus 10.8 g/day (M) 84.2 versus 22.7 g/day (W) Per 50 g/day | 0.87 (0.68–1.12) Ptrend: 0.07 0.91 (0.82–1.01) (calibrated) 0.97 (0.90–1.04) (observed) | Age, sex, BMI, center, educational level, energy intake, physical activity, total vegetable consumption, alcohol intake, other fruits, red and processed meat, smoking, other fresh fruits |
Never smokers Former smokers Current smokers | Highest versus lowest Per 50 g/day Highest versus lowest Per 50 g/day Highest versus lowest Per 50 g/day | (0.64–1.51) 1.00 (0.90–1.11) 0.90 (0.57–1.40) 1.01 (0.90–1.14) 0.69 (0.44–1.10) 0.86 (0.74–1.01) | ||||||
201 | Gastric cardia AC | 103.6 versus 10.8 g/day (M) 84.2 versus 22.7 g/day (W) Per 50 g/day | 0.61 (0.38-1.00) Ptrend: 0.01 0.82 (0.64–1.05) (calibrated) 0.85 (0.71–1.02) (observed) | |||||
323 | Gastric non-cardia AC | 103.6 versus 10.8 g/day (M) 84.2 versus 22.7 g/day (W) Per 50 g/day | 1.25 (0.86–1.80) Ptrend: 0.46 0.99 (0.85–1.15) (calibrated) 1.03 (0.95–1.13) (observed) | |||||
Steevens, 2011, Netherlands [26] | NLCS Case cohort Age: 55–69 years | 1986–2002 (16.3) | 4 035 Men and women, 156 | Validated FFQ, 150 food items, fresh lemon juice, grapefruits, grapefruit juice, mandarins, oranges, fresh orange juice | Incidence Gastric cardia AC | 156 versus 0 g/day Per 25 g/day | 0.38 (0.21–0.69) Ptrend: 0.003 0.88 (0.81–0.97) | Age, sex, smoking status, cigarettes/day, smoking duration, alcohol, red meat, fish, vegetable, all other fruits |
460 | Gastric non-cardia AC | 156 versus 0 g/day Per 25 g/day | 0.80 (0.56–1.15) Ptrend: 0.46 0.99 (0.95–1.03) | |||||
Li, 2010, Japan [25] | NHI Prospective cohort Age: 40–79 years | 1995–2003 (9) | 42 470 Men and women, 806 | Validated FFQ, 40 food items, citrus fruit | Incidence Gastric cancer | ≥7 versus ≤2 times/week | 0.99 (0.80–1.21) Ptrend: 0.90 | Age, sex, BMI, smoking, alcohol, employment, education, walking, exercise or sports, diabetes, gastric ulcer, hypertension, family history of cancer, energy intake, intake of tea, coffee, miso soup, rice, soybean, dairy products, fish, meat, vegetables, and other fruits |
Epplein, 2010, China [28] | SMHS Prospective cohort Age: 40–74 years | 2002/2006–2007 (3.6) | 59 247 Men, 132 | Validated FFQ, 81 food items, tangerines, oranges, grapefruit | Incidence Distal (i.e., non-cardia) gastric cancer | >18.0 versus ≤1.6 g/day | 0.70 (0.41–1.18) Ptrend: 0.34 | Age, education level, smoking, total energy intake |
SWHS Prospective cohort Age: 40–70 years | 1996/2000–2007 (9.2) | 73 064 Women, 206 | Validated FFQ, 77 food items, tangerines, oranges, grapefruit | >31.9 versus ≤ 6.1 g/day | 0.94 (0.62–1.42) Ptrend: 0.86 | |||
Freedman, 2008, USA [17] | NIH-AARP Prospective cohort Age: 50–71 years Retired | 1995/1996–2000 (4.5) | 490 802 Men and women, 198 | Validated FFQ, 124 food items, oranges, tangerines, tangelos, grapefruits | Incidence Gastric cardia cancer | 1.12 versus 0.08 serving/1,000 kcal | 0.88 (0.62–1.23) | Age, sex, BMI, ethnicity, alcohol intake, cigarette dose, education, total energy, usual activity throughout the day, vigorous physical activity |
196 | Gastric non-cardia cancer | 1.36 (0.96–1.94) | ||||||
Iso, 2007, Japan [24] | JACC Prospective cohort Age: 40–79 years | N/A-2003 (15) | 43 011 Men, 715 | Validated FFQ, 39 food items, citrus fruit | Mortality Gastric cancer | ≥5 versus <3 times/week | 1.06 (0.86–1.30) | Age, area of study |
59 504 Women, 344 | 1.29 (0.95–1.74) | |||||||
McCullough, 2001, USA [29] | CPS II Prospective cohort Age: 30 years | 1982–1996 (14) | 436 654 Men, 910 | FFQ, 32 food items, citrus fruit, juices | Mortality Gastric cancer | >7 versus 0–1.9 times/week | 0.88 (0.75–1.03) | Age, BMI, educational level, family history of stomach cancer, multivitamin supplement, smoking habits, aspirin use, ethnicity/race, vitamin C supplement |
533 391 Women, 439 | >7 versus 0–2.9 times/week | 0.97 (0.78–1.21) |
Cancer type | Esophageal cancer | Esophageal squamous cell carcinoma | Esophageal adenocarcinoma | Esophageal adenocarcinoma, gastric cardia | Gastric cancer | Gastric cardia cancer | Gastric non-cardia cancer |
---|---|---|---|---|---|---|---|
Linear dose–response meta-analysis per 100 g/day
| |||||||
No. of studies | 6 | 3 | 3 | 3 | 6 | 3 | 4 |
No. of cases | 1,057 | 320 | 422 | 1,348 | 4,907 | 555 | 1,317 |
Person-years | 7,513,150 | 2,542,187 | 5,354,570 | 7,507,530 | 22,949,089 | 7,507,530 | 8,393,008 |
RR (95 % CI) | 0.86 (0.74–1.00) | 0.87 (0.69–1.08) | 0.93 (0.78–1.11) | 0.83 (0.67–1.02) | 0.95 (0.85–1.05) | 0.75 (0.55–1.01) | 1.02 (0.90–1.16) |
I
2, P
heterogeneity
| 0 %, 0.83 | 23 %, 0.27 | 0 %, 0.58 | 50 %, 0.14 | 31 %, 0.21 | 55 %, 0.11 | 2 %, 0.40 |
Highest versus lowest analysis
| |||||||
No. of studies | 7 | 3 | 3 | 3 | 6 | 3 | 4 |
No. of cases | 1 158 | 320 | 422 | 1 348 | 4 907 | 555 | 1 317 |
RR (95 % CI) | 0.77 (0.64–0.91) | 0.65 (0.47–0.89) | 0.78 (0.56–1.09) | 0.67 (0.44–1.01) | 0.95 (0.83–1.08) | 0.62 (0.39–0.99) | 1.01 (0.79–1.28) |
I
2, P
heterogeneity
| 5 %, 0.39 | 0 %, 0.60 | 29 %, 0.24 | 77 %, 0.01 | 57 %, 0.04 | 67 %, 0.05 | 47 %, 0.11 |
Esophageal cancer
Per 100 g/day | Esophageal cancer | Gastric cancer | ||||||
---|---|---|---|---|---|---|---|---|
N
| RR (95 % CI) |
I
2 (%) |
P
heterogeneity
|
N
| RR (95 % CI) |
I
2 (%) |
P
heterogeneity
| |
All studies | 6 | 0.86 (0.74–1.00) | 0 | 0.83 | 6 | 0.95 (0.85–1.05) | 31 | 0.21 |
Sex | ||||||||
Men | 2 | 0.93 (0.70–1.24) | 0 | 0.34 | 2 | 0.91 (0.76–1.09) | 8 | 0.30 |
Women | 1 | 0.63 (0.08–5.23) | – | – | 2 | 1.20 (0.67–2.15) | 65 | 0.09 |
Outcome type | ||||||||
Incidence | 5 | 0.85 (0.73–0.99) | 0 | 0.84 | 4 | 0.93 (0.82–1.07) | 23 | 0.27 |
Mortality | 1 | 1.27 (0.51–3.17) | – | – | 2 | 1.03 (0.73–1.46) | 70 | 0.07 |
Geographic location | ||||||||
Asia | 3 | 0.87 (0.67–1.13) | 0 | 0.45 | 2 | 1.10 (0.85–1.41) | 21 | 0.26 |
Europe | 2 | 0.80 (0.57–1.13) | 0 | 0.54 | 2 | 0.84 (0.71–0.98) | 0 | 0.86 |
North America | 1 | 0.88 (0.70–1.11) | – | – | 2 | 0.97 (0.81–1.16) | 55 | 0.13 |
Europe and North America | 3 | 0.86 (0.71–1.04) | 0 | 0.75 | 4 | 0.91(0.82–1.02) | 23 | 0.28 |
Duration of follow-up | ||||||||
<10 years | 4 | 0.85 (0.72–1.02) | 0 | 0.70 | 2 | 1.05 (0.89–1.23) | 0 | 0.62 |
≥10 years | 2 | 0.88 (0.63–1.24) | 0 | 0.40 | 4 | 0.90 (0.79–1.03) | 32 | 0.22 |
Number of cases | ||||||||
<100 | 1 | 0.59 (0.21–1.65) | – | – | – | |||
100–<200 | 3 | 0.87 (0.67–1.13) | 0 | 0.45 | – | |||
200–<500 | 2 | 0.87 (0.71–1.05) | 0 | 0.81 | 1 | 1.08 (0.88–1.31) | – | – |
500–<1,000 | – | 3 | 0.87 (0.76–1.00) | 0 | 0.60 | |||
≥1,000 | – | 2 | 1.03 (0.73–1.46) | 70 | 0.07 | |||
Publication year | ||||||||
<2,010 | 4 | 0.89 (0.74–1.06) | 0 | 0.75 | 3 | 1.02 (0.85–1.24) | 56 | 0.10 |
≥2,010 | 2 | 0.78 (0.57–1.08) | 0 | 0.47 | 3 | 0.87 (0.76–1.00) | 0 | 0.60 |
Adjustment for confounders
| ||||||||
Socioeconomic status | ||||||||
Yes | 3 | 0.84 (0.68–1.04) | 0 | 0.52 | 4 | 0.93 (0.83–1.04) | 21 | 0.29 |
No | 3 | 0.89 (0.71–1.11) | 0 | 0.70 | 2 | 1.02 (0.69–1.53) | 69 | 0.07 |
Smoking | ||||||||
Yes | 5 | 0.85 (0.73–0.99) | 0 | 0.84 | 5 | 0.92 0.84–1.01 | 4 | 0.39 |
No | 1a
| 1.27 (0.51–3.17) | – | – | 1a
| 1.29 0.89–1.85 | – | – |
Alcohol intake | ||||||||
Yes | 5 | 0.85 (0.73–0.99) | 0 | 0.84 | 4 | 0.93 (0.82–1.07) | 23 | 0.27 |
No | 1a
| 1.27 (0.51–3.17) | – | – | 2b
| 1.03 (0.73–1.46) | 70 | 0.07 |
BMI | ||||||||
Yes | 3 | 0.84 (0.68–1.04) | 0 | 0.52 | 4 | 0.93 (0.83–1.04) | 21 | 0.29 |
No | 3 | 0.89 (0.71–1.11) | 0 | 0.70 | 2 | 1.02 (0.69–1.53) | 69 | 0.07 |
Physical activity | ||||||||
Yes | 3 | 0.84 (0.68–1.04) | 0 | 0.52 | 3 | 0.96 (0.81–1.13) | 39 | 0.20 |
No | 3 | 0.89 (0.71–1.11) | 0 | 0.70 | 3 | 0.94 (0.78–1.14) | 46 | 0.16 |
Total energy intake | ||||||||
Yes | 3 | 0.84 (0.68–1.04) | 0 | 0.52 | 3 | 0.96 (0.81–1.13) | 39 | 0.20 |
No | 3 | 0.89 (0.71–1.11) | 0 | 0.70 | 3 | 0.94 (0.78–1.14) | 46 | 0.16 |
Ethnicity | ||||||||
Yes | – | 2 | 0.97 (0.81–1.16) | 55 | 0.13 | |||
No | 6 | 0.86 (0.74–1.00) | 0 | 0.83 | 4 | 0.93 (0.79–1.11) | 37 | 0.19 |